Breaking the loop in AML.

Abstract

In this issue of Blood1, Bamezai et al reveal an unexpected, moonlighting* function of the germ cell associated RNA binding protein, PIWIL4 in AML. The authors show a tumor-specific requirement for PIWIL4 in R-loop homeostasis. Loss of PIWIL4 in AML cells led to uncontrolled R-loop formation, transcriptional stalling, DNA damage and an enhanced sensitivity to ATR inhibition, findings that may inform future therapeutic approaches.